Analysis of in vivo turnover of tau in a mouse model of tauopathy

摘要: Background Intracellular accumulation of tau as neurofibrillary tangles (NFTs) is the hallmark Alzheimer’s disease (AD) well in other tauopathies. Tau present not only cytoplasm but also extracellular space such cerebrospinal fluid (CSF) and brain interstitial (ISF). Although clearance one critical parameter leading to intracellular/extracellular accumulation, vivo turnover has been characterized. The current study attempted precisely determine rates utilizing tet-off regulatable mice. In particular, we assessed intracellular tau, soluble insoluble phosphorylated at certain sites a combination microdialysis, biochemical analysis specific ELISAs recognizing each species. To examine effect tauopathy-associated mutation on clearance, half-lives various species were compared between mice with FTDP-17 that induces β-sheet formation, ΔK280 (pro-aggregant mice) control additional breaking mutations (anti-aggregant mice).